Water is an essential component of all life, and maintaining water balance is a key component of physiological homeostasis. The humidity of the air determines how rapidly water evaporates, and is thus a critical environmental variable. Insects are particularly vulnerable to changes in body water from evaporation because of their small size and large surface area to volume ratio, and so possess sensitive hygro-sensory systems that allow them to seek out environments of appropriate moisture and avoid excessively dry or moist regions. From a human health perspective, insect disease vectors use hygrosensing to locate hosts. Field studies indicate that moisture can be as powerful an attractive cue for Aedes females, as temperature and carbon dioxide. Despite the importance of hygrosensing to human health and insect biology, its molecular and cellular basis remains poorly understood. While humidity is a function of the concentration of water vapor, the key humidity-dependent parameter that governs hygrosensory responses has remained elusive. Three distinct humidity-dependent stimuli: evaporation rate, moisture-dependent pressure changes and evaporative cooling have each been proposed to underlie hygrosensation. In each model, the stimulus would activate a distinct sensory modality, evaporation rate activating chemoreceptors, pressure activating mechanoreceptors and cooling activating thermoreceptors. However, the precise stimulus or combination of stimuli involved is unclear. Our preliminary data suggests functional overlap between the molecular sensors required for sensing moisture and cold temperatures. My work not only provides a foundation for identification of molecular cold and moisture sensors, but also suggests that awareness of cooling may be critical to hygrosensing. I propose to begin to identify the underlying basis of hygrosensing by further elucidating the critical receptors for moisture in Drosophila melanogaster and using the molecular genetic tools of the fly to probe their molecular and cellular properties. This work addresses basic questions in neuroscience and sensory biology, with relevance to the survival of insect vectors of human disease and their ability to seek hosts.